Introduction

External genital warts, also known as condylomata acuminata are extremely common and is
considered as a common form of sexually stransmitted diseases affecting the general population.
There are more than 120 distinct subtypes of the human papilloma virus that have been identified,
with approximately 40 different subtypes capable of infecting the anogenital tract.

HPV can be subdivided into the following three categories: low risk, intermediate risk and high risk.
This is based on the likelihood of inducing intraepithelial dysplasias. HPV types 6 and 11 rarely give
rise to cervical cancers and are thus considered low-risk subtypes. Infection by these genotypes is
responsible for 90% of the cases of genital wart formation. In contrast, HPV types 16 and 18 are
strongly associated with cervical dysplasia and are therefore considered to be high risk, oncogenic
subtypes. Patients with condyloa acuminata may be infected simultaneously by multiple HPV strains.

Virology

HPV is a group of DNA viruses. Viral replication is restricted to the basal cell layer of surface tissues.
The virus will penetrate both the cutaneous and mucosal epitheliam in search of the appropriate cell
host. It will invade and infect the basal keratonicyte of the epidermis. The mucose can be infected
anywhere alonen the genital tract, including the vulva, vagina, cervix and perianal regions in females
as well as the penile shaft, scrotum, periurethral and perianal regions in males. Infected regions will
be marked by a proliferation of viral DNA and the formation of a warty papule or plaque.

Low risk HPV  remain sperate from the host cell DNA and undergo replication independently
High risk HPV  incorporate their DNA directly into the host cell’s genetic material. This can result in
dysregulation and promotes oncoproteins. These will bind and inactivate p53 genes and Rb  leading
to increased cell proliferation and a greater risk for malignancy

98% of its transmission is through sexual contact. Besides sexual contact, there is also a possibility of
being transmitted through items that contain the human papilloma virus.

Dermatopathology

The hallmark of an HPV infected cell is the development of atypical keratinocytes known as koilocytes.
They are enlarged cells with eccentric, pyknotic nuclei that are often surrounded by a perinuclear halo.
The epidermis will show a marked acanthosis with varying degrees of papillomatosis, hyperkeratosis
and parakeratosis and complete effacement of the granular cell layer.

Definite diagnosis can best be made through the use of electron microscopy and
immunohistochemical peroxidase-antiperoxidase stain.

Clinical Presentation

Once infected with HPV, the virus typically requires an incubation period ranging anywhere from 3
weeks to 8 months prior to clinical manifestation. On average, physical symptoms begin 2-3 months
after initial contact. The virus is cabaple of lying dormant within epithelial cells for long periods of
time. Infection may persist undetected for the duration of an individual’s lifetime with no
manifestation of clinically apparent warts.

CA may increase in number or size or even undergo a spontaneous regression. 30% of all warts will
regress within the first four months. Unfortunately, the majority of genital will recur within three
months of infection even after going through treatment. Risk for long-term wart persistence:

 Host immunosuppression
 Infection with high risk HPV subtypes
 Older patients

EGW will present on the moist tissues of the anogenital area, and may occasionally develop in the
mouth or the throat after oral sexual contact with an infected parter. CA have a highly variable
appearance and may be flat, dome shaped, cauliflower shaped or pedunculated. It can manifest
individually, as a solitary keratotic papule or plaque, but are more frequently found in large clusters.
They will begin as a small, nondistinctive 1 to 2 mm flesh colored papules on the skin and may stay
this way for the majority of the infection. It may also grow as large as several centimeters in diameter
leading to painful disruption of sexual intercourse and childbirth. It may range from the color white to
pink, purple, red or brown, it can be flat or verrucous.

Lesions are usually not painful, but patients mostly complain of:

 Severe discomfort
 Burning
 Pruritis
 Larger lesions  bleeding and irritation

Biopsy is rarely needed to diagnose, but it is recomended for lesions suspected of being malignant or
having an increased malignant potention. This includes lesions that are ulcerated, sudden change in
apperance.
Complications of Untreated HPV Infection

Both low risk and high risk HPV subtypes have also been associated with the very low grade, well
differentiated squamous cell carcinoma known as verrucous carcinoma.

Verrucous carcino tend to spread by local invasion and rarely metastasize. It is hypothesized that HPV’s
viral oncogene expression promotes the degradation of the p53 tumor suppression gene, thereby
lowering the threshold for tumor formation.

Additionally, while most HPV infections clear spontaneously, in 10 to 20% of women these infections
persist and these females are at risk for progression to grade 2/3 cervical intraepithelial neoplasms
and if left untreated can eventually develop invasive cancer of the cervix. Penile cancer, which is 10
times less common than cervical cancer also has a high correlation rate with high risk HPV infection
and history of EGW.

Another study showed that there was a significant increased risk of both anogenital cancers and
cancers of other sites among patients with genital warts. However the elevated risks of smoking
related cancers, liver, lung, prostate and kidney cancers may indicate differences in exposure and risk
factors in patients with genital warts compared to the general population. Condyloma acuminata are
strongly associated with increased risk of cancers of the vulva, vagina, penis and anus but not invasive
cervical cancer.

Yanofsky VR et al. Genital Warts: a comprehensive review. J clin Aesthet Dermatol. 2012 Jun; 5(6): 25-
36.